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The contribution of environmental pollutants to the obesity pandemic is still not yet fully recognized. Elucidating possible cellular and molecular mechanisms of their effects is of high importance. Our study aimed to evaluate the effect of chronic, 21-day-long, 2,2-bis (4-chlorophenyl)-1,1-dichlorethylenedichlorodiphenyldichloroethylene (p,p′-DDE) exposure of human adipose-derived mesenchymal stem cells committed to adipogenesis on mitochondrial oxygen consumption on days 4, 10, and 21. In addition, the mitochondrial membrane potential (MMP), the quality of the mitochondrial network, and lipid accumulation in maturing cells were evaluated. Compared to control differentiating adipocytes, exposure to p,p′-DDE at 1 μM concentration significantly increased basal (routine) mitochondrial respiration, ATP-linked oxygen consumption and MMP of intact cells on day 21 of adipogenesis. In contrast, higher pollutant concentration seemed to slow down the gradual increase in ATP-linked oxygen consumption typical for normal adipogenesis. Organochlorine p,p′-DDE did not alter citrate synthase activity. In conclusion, in vitro 1 μM p,p′-DDE corresponding to human exposure is able to increase the mitochondrial respiration per individual mitochondrion at the end of adipocyte maturation. Our data reveal that long-lasting exposure to p,p′-DDE could interfere with the metabolic programming of mature adipocytes.

Background Children are exposed to p,p’- dichlorodiphenyltrichloroethane ( p,p’- DDT) and p,p’- dichlorodiphenyldichloroethylene ( p,p’- DDE) through placental and lactational transfer. Some studies have suggested that early-life exposure to these compounds could lead to increased body mass index (BMI) during childhood. Our aim was to assess whether children’s exposure during the first 2 years of life is associated with BMI z-score in Japanese children at 42 months of age. Methods We used data from a birth cohort ( n  = 290) of the Tohoku Study of Child Development. p,p’- DDT and p,p’- DDE levels were measured in breast milk samples collected 1 month after birth, and levels in children were estimated using a toxicokinetic model for three exposure periods (0–6 months, 6–12 months, 12–24 months). Associations between exposure estimates and BMI z-score at 42 months of age were assessed using multivariate linear regression models. Results We found no significant association between levels of p,p’- DDT measured in breast milk or estimated in children and BMI z-score. However, we observed associations between estimated p,p’- DDE levels in girls during all postnatal exposure periods and BMI z-score; for each log increase in the estimated p,p’- DDE levels, BMI z-score increased by 0.23 (C.I. 95%: 0.01, 0.45) for the 0–6 months exposure period, 0.26 (C.I. 95%: 0.06, 0.47) for the 6–12 months exposure period, and 0.24 (C.I. 95%: 0.05, 0.43) for the 12–24 months exposure period. Conclusion In this study of Japanese children, estimated postnatal p,p’- DDE levels were associated with increased BMI z-score at 42 months of age, mostly in girls. These results are in line with previous studies supporting that early-life exposure to p,p’- DDE may be associated with higher BMI during childhood.

Background: Previous studies of DDT and breast cancer assessed exposure later in life when the breast may not have been vulnerable, after most DDT had been eliminated, and after DDT had been banned. Objectives: We investigated whether DDT exposure in young women during the period of peak DDT use predicts breast cancer. Methods: We conducted a prospective, nested case-control study with a median time to diagnosis of 17 years using blood samples obtained from young women during 1959-1967. Subjects were members of the Child Health and Development Studies, Oakland, California, who provided blood samples 1-3 days after giving birth (mean age, 26 years). Cases (n = 129) developed breast cancer before the age of 50 years. Controls (n = 129) were matched to cases on birth year. Serum was assayed for p,p'-DDT, the active ingredient of DDT; o,p'-DDT, a low concentration contaminant; and p,p'-DDE, the most abundant p,p'-DDT metabolite. Results: High levels of serum p,p'-DDT predicted a statistically significant 5-fold increased risk of breast cancer among women who were born after 1931. These women were under 14 years of age in 1945, when DDT came into widespread use, and mostly under 20 years as DDT use peaked. Women who were not exposed to p,p'-DDT before 14 years of age showed no association between p,p'-DDT and breast cancer (p = 0.02 for difference by age). Conclusions: Exposure to p,p'-DDT early in life may increase breast cancer risk. Many U.S. women heavily exposed to DDT in childhood have not yet reached 50 years of age. The public health significance of DDT exposure in early life may be large.

Background: We previously reported associations between organochlorines and behaviors related to attention deficit hyperactivity disorder among boys and girls at 8 years of age using a teacher's rating scale for a birth cohort in New Bedford, Massachusetts (USA). Objectives: Our goal was to corroborate these findings using neuropsychological measures of inattentive and impulsive behaviors. Methods: We investigated the association between cord serum polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) and attention and impulse control using a Continuous Performance Test (CPT) and components of the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III). Participants came from a prospective cohort of children born during 1993–1998 to mothers residing near a PCB-contaminated harbor in New Bedford. Median (range) cord serum levels for the sum of four prevalent PCBs [congeners 118, 138, 153, and 180 (ΣPCB₄)] and p,p'-DDE were 0.19 (0.01–2.59) and 0.31 (0–14.93) ng/g serum, respectively. Results: We detected associations between PCBs and neuropsychological deficits for 578 and 584 children with CPT and WISC-III measures, respectively, but only among boys. For example, boys with higher exposure to ΣPCB₄ had a higher rate of CPT errors of omission [rate ratio for the exposure interquartile range (IQR) = 1.12; 95% confidence interval (CI): 0.98, 1.27] and slower WISC-III Processing Speed (change in score for the IQR = –2.0; 95% CI: –3.5, –0.4). Weaker associations were found for p,p'-DDE. For girls, associations were in the opposite direction for the CPT and null for the WISC-III. Conclusions: These results support an association between organochlorines (mainly PCBs) and neuropsychological measures of attention among boys only. Sex-specific effects should be considered in studies of organochlorines and neurodevelopment.

Background Exposure to the bioaccumulative pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) has been associated with increased risk of insulin resistance and obesity in humans and experimental animals. These effects appear to be mediated by reduced brown adipose tissue (BAT) thermogenesis, which is regulated by the sympathetic nervous system. Although the neurotoxicity of DDT is well-established, whether DDT alters sympathetic innervation of BAT is unknown. We hypothesized that perinatal exposure to DDT or DDE promotes thermogenic dysfunction by interfering with sympathetic regulation of BAT thermogenesis. Methods Pregnant C57BL/6 J mice were administered environmentally relevant concentrations of DDTs (p,p’-DDT and o,p’-DDT) or DDE (p,p’-DDE), 1.7 mg/kg and 1.31 mg/kg, respectively, from gestational day 11.5 to postnatal day 5 by oral gavage, and longitudinal body temperature was recorded in male and female offspring. At 4 months of age, metabolic parameters were measured in female offspring via indirect calorimetry with or without the β3 adrenergic receptor agonist, CL 316,243. Immunohistochemical and neurochemical analyses of sympathetic neurons innervating BAT were evaluated. Results We observed persistent thermogenic impairment in adult female, but not male, mice perinatally exposed to DDTs or p,p’-DDE. Perinatal DDTs exposure significantly impaired metabolism in adult female mice, an effect rescued by treatment with CL 316,243 immediately prior to calorimetry experiments. Neither DDTs nor p,p’-DDE significantly altered BAT morphology or the concentrations of norepinephrine and its metabolite DHPG in the BAT of DDTs-exposed mice. However, quantitative immunohistochemistry revealed a 20% decrease in sympathetic axons innervating BAT in adult female mice perinatally exposed to DDTs, but not p,p’-DDE, and 48 and 43% fewer synapses in stellate ganglia of mice exposed to either DDTs or p,p’-DDE, respectively, compared to control. Conclusions These data demonstrate that perinatal exposure to DDTs or p,p’-DDE impairs thermogenesis by interfering with patterns of connectivity in sympathetic circuits that regulate BAT. Graphical abstract

Many of South Africa’s freshwater impoundments are compromised by pesticide pollution, and the Roodeplaat Dam, near Pretoria, is no exception. This paper is, to the best of our knowledge, the first report of the herbicides Dacthal, metribuzin, simazine, tebuthiuron, terbuthylazine, and the fungicides azoxystrobin, carbendazim, epoxiconazole, metalaxyl (Ridomil), propiconazole, pyrimethanil and thiabendazole in a South African freshwater impoundment. This short note reports on the screening results of water and muscle tissue samples against a comprehensive library of pesticides, herbicides and fungicides in the polluted Roodeplaat Dam. Muscle samples of Oreochromis mossambicus screened positive for p,p' -DDE and p,p' -DDD and for DCPA (chlorthal-methyl). The muscle tissue of Clarias gariepinus screened positive for p,p'- DDE and p,p'- DDD, chlorpyrifos, trans -chlordane, DCPA and terbuthylazine. The presence of these pesticides, herbicides and fungicides in this impoundment is of great concern as there is substantial evidence of adverse health effects in fish exposed to these chemicals.

Prenatal exposure to dichlorodiphenyldichloroethylene (p,p´-DDE) may interfere with fetal development; however, studies evaluating anthropometry and gestational age at birth show inconsistent results. Typically, p,p´-DDE exposure has been measured during the third trimester and missed the key early pregnancy period. We evaluated the association between p,p´-DDE exposure before week 18 of pregnancy and anthropometry at birth, as well as gestational length, in 170 mother–child pairs from a cohort study in a flower-growing mexican region. Maternal serum p,p´-DDE concentrations were determined by gas chromatography. The associations between p,p´-DDE and z-scores of birth weight, birth length, and gestational age were evaluated by linear multiple regression models. Logistic regression models were used for low birth weight and small size for gestational age. Effect modification by child’s sex was explored. The average gestational age at the blood sample extraction was 10.6 weeks. p,p'-DDE was detected in 64.7% of mothers, at a geometric mean of 0.24 ng/mL. Prenatal p,p´-DDE exposure was not associated with the birth outcomes in the whole sample. However, a high p,p´-DDE exposure was marginally associated with greater small for gestational age risk in male newborns (OR≥0.076 ng/mL vs <0.076 ng/mL = 3.09, 95% CI: 0.61; 15.58), but not in female (p for interaction = 0.08). Even though, we found no reductions in anthropometric measurements or gestational length associated with early prenatal p,p´-DDE exposure, the potential effect modification by infant’s sex in terms of small for the gestational age risk deserves future studies.

Background: Evidence suggests that p,p'-dichlorodiphenyldichloroethene (DDE) affects neurodevelopment in infants, although a critical exposure window has not yet been identified. Objectives: Our goal was to assess the prenatal DDE exposure window and its effect on the psychomotor development index (PDI) and mental development index (MDI) during the first year of life. Methods: We recruited 244 children whose pregnancies and deliveries were uncomplicated, and whose mothers were monitored throughout the pregnancy. Participating mothers were not occupationally exposed to DDT (dichlorodiphenyltrichloroethane) but were residents of a zone in Mexico with endemic malaria. We measured serum levels of DDE before pregnancy and during each trimester of the pregnancy. We evaluated PDI and MDI of the Bayley Scales for Infant Development (BSID-II), at 1, 3, 6, and 12 months of age. We adjusted for quality of the home environment and maternal intellectual coefficient (IQ). We used generalized mixed-effects models for statistical analysis. Results: Third-trimester DDE level (7.8 ± 2.8 ppb) was significantly higher than the level at baseline, first, and second trimesters, but the differences never exceeded 20%. Only DDE levels during the first trimester of pregnancy were associated with a significant reduction in PDI (every doubled increase of DDE level reduced the PDI 0.5 points). DDE was not associated with MDI. Conclusions: A critical window of exposure to DDE in utero may be the first trimester of the pregnancy, and psychomotor development is a target of this compound. Residues of DDT metabolites may present a risk of developmental delay for years after termination of DDT use.

Diaion® HP-20 resin passive samplers deployed in water and sediment samples collected from Lake Ziway were analyzed for 30 organochlorine, organophosphorus, carboxamide, and pyrethroid pesticide residues. The samples were collected from purposely selected sampling stations in five sites on Lake Ziway. Levels of selected pesticides were determined by GC–MS/MS in all samples. p,p′DDE and boscalid residues were the only detected pesticides in sediment samples. Similarly, only metalaxyl and boscalid residues were recovered from HP-20 resins. The concentration of p,p′DDE and boscalid in sediment ranged from 0.66–7.23 and 0.1–15.26 ng g −1 dry weight respectively. The presence of p,p′DDE but no other metabolites of DDT in all sediment samples indicated that DDT residues in Ziway Lake were aged and probably originated from the weathered agricultural soils of the surrounding region. The highest level of boscalid was recorded at Site 2 (near the floriculture enterprises) both in sediment and in HP-20 resins with a mean concentration of 11.8 ng g −1 dw and 39.6 ng g −1 disk respectively. However, the concertation of metalaxyl was the highest in the HP-20 resins deployed at Site1 and Site 4 (near the intensive small-scale vegetable farm) with a mean concentration of 54.7 ng g −1 disk and 54.3 ng g −1 disk respectively. Generally, most sampling sites of p,p′DDE were found to have a moderate ecological risk based on levels specified in the sediment quality standards. Moreover, the relatively high boscalid and metalaxyl levels in HP-20 deployed in Lake Ziway would be the result of recent intensive pesticide use by floriculture enterprises and small-scale vegetable farmers in the region. A spatial variation on the accumulation of detected pesticides among the sampling sites depends on the anthropogenic activities, around the lake from the point and non-point sources. Although most of the analyzed pesticides were below the detectable limit, further studies and continued monitoring of currently used pesticide residues in the Lake are highly recommended.

BACKGROUND: Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants, for which animal studies demonstrate immunotoxic effects, including thymic atrophy and suppressed immune responses; human investigations of similar end points are sparse. The thymus is essential for the differentiation and maturation of T-cell lymphocytes. OBJECTIVES: The objective of this study was to examine the association between prenatal PCB exposures and estimated thymus volume in infants from eastern Slovakia, a region where PCBs were produced until 1984. METHODS: Mothers were enrolled at delivery, and maternal blood samples were collected for analysis of 15 PCB congeners, p,p'-DDT [1,1,1-trichloro-2,2'-bis(p-chlorophenyl)ethane], and p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene]. Each mother was interviewed to obtain information on sociodemographic characteristics, past pregnancies, occupational history, medication history, and living environment. Neonatal thymus volume was estimated using ultrasound measurements on the third or fourth day after birth. Thymic index was calculated on 982 newborns from mothers with PCB measurements. We developed a predictive model of the natural log of the thymic index using multiple linear regression with covariates selected from the bivariate analyses. RESULTS: Prenatal PCB exposure was associated with a smaller thymic index at birth [β = -36 (natural log-transformed; nanograms per gram lipids); p = 0.047]. District of residence and delivery also predicted thymic index. Male sex, later gestational age, larger birth weight z-score, and Roma ethnicity were associated with a larger thymic index, whereas respiratory illness was associated with a lower thymic index. CONCLUSIONS: This study provides the first evidence to date that PCB exposure in neonates is associated with a smaller thymic volume, suggesting possible impaired immunologic development.